Technical Field
The present disclosure relates to a syringe that is used to inject a small amount of drug solution such as a vaccine into an upper layer of skin, and particularly into a target site near an epidermic layer in a dermic layer.
Background Art
A drug solution including a biological preparation such as an influenza vaccine is generally subcutaneously administered to subcutaneous tissue of skin, or intramuscularly administered to muscle tissue deeper than the subcutaneous tissue. Recently, it has been revealed that the dose of the vaccine can be reduced by administering the vaccine to an upper layer of skin, that is, a target site, ranging from epidermis to dermis where many immunocompetent cells are present.
Skin includes an epidermic layer having a thickness of 50 to 200 μm from a skin surface, a dermic layer having a thickness of 0.5 to 3.5 mm continuing from the epidermic layer, and a subcutaneous tissue layer deeper than the dermic layer. The immunocompetent cells such as Langerhans cells that exist in an epidermis stratum spinosum layer within the epidermic layer and many intradermal dendritic cells that exist near the epidermic layer in the dermic layer are provided with dendritic projections, have receptors that are responsible for skin immunity, and react to antigens from the outside.
The epidermic layer is very thin because it has the thickness of only 50 to 200 μm from the skin surface. Individual variability in the epidermic layer is large because an epidermic condition and a thickness are different depending on an age difference between adults, youths, infants, and babies, a gender difference, individual differences. Therefore, it is very difficult to selectively inject a very small amount of vaccine equal to or less than 200 μL into the epidermis stratum spinosum layer where the Langerhans cells exist by means of an injection needle much thicker than the thickness of the epidermic layer, which is the only usable injection needle in terms of strength and convenience of manufacture.
Instead of the epidermic layer, if the vaccine can be injected, so that an injection site can be selected from the upper layer of skin ranging from the epidermic layer to the dermic layer, into the epidermis stratum spinosum layer where the Langerhans cells exist or a region near the epidermis in the dermic layer where the intradermal dendritic cells exist, it should be possible to further increase immunity elicitation capability while reducing the dose of the vaccine.
Because the upper layer of skin includes a lot of elastic fibrous tissue such as elastin and collagen, the upper layer of skin is harder than the subcutaneous tissue. When a large amount of a drug solution is injected into this upper layer of skin, aching pain is felt. Therefore, an injection amount of the drug solution into the upper layer of skin needs to be a very small amount, that is, equal to or less than 200 μL, and desirably about 100 μL.
In this regard, such an efficient syringe has been studied that such a very small amount of the drug solution can be diffused into the Langerhans cells, and the vaccine is selectively injected into the site near the epidermis in the dermic layer where many intradermal dendritic cells exist to form a bulge, where the vaccine stays for a period of time.
An example of the syringe that injects a small amount of the drug solution into the dermic layer of the upper layer of skin includes a syringe in which a tubular body that accommodates a drug solution and an injection needle assembly having an injection needle are formed independently, and the injection needle assembly is mounted to a drug solution discharging tube at a tubular end of the tubular body just before the injection.
For example, JP 2011-212185 A discloses a drug injection device including: a tubular body having a fluid chamber that accommodates a drug; a pusher section including a gasket that is mounted to a plunger and moves within the tubular body; a tubular grip section provided along an outer periphery of the tubular body; a connection section between the tubular body and an end portion of the grip section; and an injection needle assembly having a needle hub that holds an injection needle, and configured to inject, into an upper layer of skin, the drug from a needle tip slightly protruding from the needle hub. Specifically, a drug solution discharging tube at a tubular end of the tubular body is pushed and mounted into a fitting hole of the injection needle assembly.